IL-37 Causes Excessive Inflammation and Tissue Damage on Murine Pneumococcal Pneumonia
IL-37 Causes Excessive Inflammation and Tissue Damage on Murine Pneumococcal Pneumonia
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DOI：
10.1159/000469661
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发表时间：
2017-01-01
影响因子：
5.3
通讯作者：
Slevogt, Hortense
中科院分区：
文献类型：
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作者：
Schauer, Anja E.;Klassert, Tilman E.;Slevogt, Hortense
肺炎链球菌感染可导致严重的并发症，过度的免疫激活和组织损伤。白细胞介素-37（IL-37）作为先天性和获得性免疫的抑制剂已经获得重要性，并且其作用已经是治疗性的，因为它们预防自身免疫性和炎性疾病中的组织损伤。通过使用人IL-37稳定转染的RAW巨噬细胞，我们显示了响应于肺炎球菌感染的内化肺炎球菌的IL-6、TNF-α和IL-1 β的细胞因子水平降低70%。在感染S.使用人IL-37 b（IL-37 tg）转基因小鼠，我们观察到肺中IL-6、TNF-α和IL-1 β的细胞因子表达的初始降低，随后是肺炎球菌负荷的晚期增强和促炎细胞因子水平的随后增加。此外，观察到肺泡巨噬细胞和中性粒细胞的募集显著增加，而IL-37 tg小鼠的肺中TRAIL mRNA减少3倍，导致坏死性肺炎，浸润性中性粒细胞的死亡增加，菌血症传播增强，死亡率增加。总之，我们已经确定IL-37调节了肺炎球菌肺炎成功炎症反应的几个核心成分，导致炎症，组织损伤和死亡率增加。(C)2017 S. Karger AG，巴塞尔。
Streptococcus pneumoniae infections can lead to severe complications with excessive immune activation and tissue damage. Interleukin-37 (IL-37) has gained importance as a suppressor of innate and acquired immunity, and its effects have been therapeutic as they prevent tissue damage in autoimmune and inflammatory diseases. By using RAW macrophages, stably transfected with human IL-37, we showed a 70% decrease in the cytokine levels of IL-6, TNF-alpha, and IL-1 beta of internalized pneumococci in response to pneumococcal infection. In a murine model of infection with S. pneumoniae, using mice transgenic for human IL-37b (IL-37tg), we observed an initial decrease in cytokine expression of IL-6, TNF-a, and IL-1 beta in the lungs, followed by a late-phase enhancement of pneumococcal burden and subsequent increase of proinflammatory cytokine levels. Additionally, a marked increase in recruitment of alveolar macrophages and neutrophils was noted, while TRAIL mRNA was reduced 3-fold in lungs of IL-37tg mice, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, enhanced bacteremic spread, and increased mortality. In conclusion, we have identified that IL-37 modulates several core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality. (C) 2017 S. Karger AG, Basel.